Term
| Non-invasive routes that avoid first-pass metabolism |
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Definition
| Sublingual, nasal, rectal, transdermal, inhalation |
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Term
| Exceptional brain areas "outside" of the BBB |
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Definition
Area postrema (vomiting center; detects toxins) Median eminance (allows hypthalamic hormones into the blood) |
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Term
pH ranges for Gastric juice small intestine blood |
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Definition
Gastric juice: pH=1-3 Small intestine: pH=5-6.6 Blood: pH=7.35-7.45 |
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Term
| As the pH of the intestine is increased from 3.5 to 8, the rate of absorption of a weak ___ increases and the rate of absoprtion of a weak ____ _____. |
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Definition
| As the pH of the intestine is increased from 3.5 to 8, the rate of absorption of a weak base increases and the rate of absorption of a weak acid decreases. |
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Term
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Definition
| alcohol -> (alcohol dehydrogenase) -> acetaldehyde -> (aldehyde dehydrogenase) -> acetic acid |
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Term
What makes a drug more potent than another? What makes a drug more effective (high efficacy)? |
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Definition
A drug is more potent if it has a higher ability to cross the BBB and has a higher affinity for the receptor. A drug has a higher efficacy if it has higher amount of intrinsic acivity at the same recepter once bound. |
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Term
| What is autoradiography and what is it used for? |
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Definition
| Autoradiography is used to look at receptor sites in a slice of brain...done by washing a radioligand over a brain section, rinsing, and then placing it on a film to visualize. |
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Term
| What is hybridization used for? |
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Definition
Hybridization is used to quantify the expression of a gene within a certain tissue. In situ hybridization is done by using a labeled probe with the correct sequence of complementary bases to an mRNA strand...after hybridized, the product labels the cell that contains the genetic code for the protein of interest. |
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Term
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Definition
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Term
| What is immunocytochemistry? |
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Definition
| Technique that uses antibodies to locate a specific antigen on a neuron, such as a protein, neuropeptide, or neurotransmitter. |
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Term
| What are immediate-early genes? and what is an example? |
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Definition
| Genes that are activated rapidly and transiently in response to a stimulus (such as a drug). Fos is an example...but located fos expression, one is able to see what cells are being activated by a particular drug. |
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Term
| What is microdialysis and voltammetry? |
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Definition
They are both in vivo stereotaxic procedures. Microdialysis involves measuring chemicals/NTs in the CSF (minute by minute resolution). Voltammetry measures NT release via implanted electrode (second by second resolution). |
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Term
| Describe positive and negative reinforcement and punishment. |
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Definition
Positive reinforcement=presentation increases the probability of a behavior Negative reinforcement=removal increases the probability of a behavior Punishment=presentation decreasesthe probability of a behavior |
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Term
| What are DRL (differential reinforcement of low rate) schedules? |
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Definition
| Get reinforcement after a fixed time, but if rat responds before the time is up, there is a "time out" and the lock is reset |
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Term
| electrical synapses are formed by |
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Definition
| Electrical synapses formed by connexins and pannexins (gap junctions) and are bidirectional. |
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Term
Classical NTs Non-classical NTs |
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Definition
Classical NTs Amino acids (Glutamate, GABA, Glycine) Monoamines (DA, NE, 5-HT) ACh Non-classical NTs Neuropeptides (Endorphins and Enkelphalins, Corticotropin releasing-factor CRF, others) Lipids (Anandamide) Gases (NO)
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Term
Where are neuropeptide transmitters (enkelphalins, endorphins, CRF) synthesized? Where are classical NTs synthesized? |
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Definition
Neuropeptide transmitters synthesized in the cell body. Classical NTs are systhesized in the axon terminal. |
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Term
What is Synaptotagmin? What is SNARE? How does botulinum toxin (Botox) work? |
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Definition
Synaptotagmin is the key Ca2+ sensory synaptic protein. SNARE is a protein that mediates the fusion of the NT vesicle with the plasma membrane to facilitate exocytosis. Botox works by cleaving proteins involved in facilitating fusion of vesicle with plasma membrane (causes paralysis). |
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Term
| What kind of receptors are GABA-A receptors? What are they activated by? |
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Definition
| GABA-A recetpros are gated Cl- channels activated by sedative-hypnotics (barbs, alcohol, BZ) |
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Term
As second messengers, cAMP causes activation of... cGMP causes activation of... Ca2+ binds to ___ which causes activation of... |
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Definition
cAMP causes activation of PKA cGMP causes activation of PKG Ca2+ binds to calmodulin which causes activation of Ca2+calmodulin-dependent protein kinases (CaMKs) |
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Term
| The catalytic subunit of PKA can cross the nuclear membrane and phosphorylate ____ in order to ___ |
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Definition
| The catalytic subunit of PKA can cross the nuclear membrane and phosphorylate CREB to increase transcription of a certain gene. |
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Term
| All neurons have receptors for ___ |
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Definition
| All neurons have receptors for glutamate |
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Term
___ packages glutamate into vesicles. ___ take up glutamate from the synaptic cleft. ___ are reliable markers of glutamatergic neurons. |
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Definition
vGLUTs package glutamate into vesicles. EAATs take up glutamate from the synaptic cleft. vGLUT1,2 are reliable markers for glutammatergic neurons. (vGLUT3 is strangely expressed in some other neuron types) |
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Term
What parts of the brain is vGLUT2 mRNA found? Where is vGLUT1 mRNA found? |
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Definition
vGLUT2 mRNA is found in the inferior colliculus, thalamus, and deep cerebellar nuclei. vGLUT1 mRNA is found in the cerebellar cortex, hippocampus, and cortex. |
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Term
The 3 ionotropic glutamate receptors (iGluRs). What is required to allow Ca2+ entry through NMDA receptors? Metabotropic glutamate receptors (mGluRs) 1 and 5 are coupled to... mGluR2,3,4,6,7&8 are coupled to... |
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Definition
AMPA, Kainate (both Na+ channels) and NMDA (Na+ and Ca2+ channel). For NMDA receptors to open and allow Ca2+ influx, glutamate must be bound and the postsynaptic neuron must be depolarized (to relieve Mg2+ blockade) mGluR1,5 are Gq-coupled with DAG 2nd messenger. mGluR2,3,4,6,7,8 are Gi/o-coupled, and reduce cAMP production. |
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Term
___ receptors are typically involved in the induction (but not expression) of LTP. In neurons exhibiting STDP, when presynaptic activity precedes the postsynaptic spike, __ in induced. ..when presynaptic activity followsthe postsynaptic spike, __ is induced. |
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Definition
NMDA receptors are typically involved in t he induction (not expression) of LTP. When presynaptic activity precedes the postsynaptic spike, LTP is induced. ..when it follows the postsynaptic spike, LTD is induced. |
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Term
Glutamate is converted to GABA by ____. What is vGAT? Whats the difference between GABAA/C receptors and GABAB receptors? |
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Definition
Glutamate is converted to GABA by glutamic acid decarboxylase (GAD). vGAT=vesicular glutamate (and glycine) transporter. GABAA/C receptors are ionotropic Cl- receptors. GABAB receptors are obligate heterodimer metabotropic receptors. |
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Term
What are the functions of the beta-gamma subunit and the alpha subunit of GABAB receptors? In most parts of the brain, the main projection cells are ______ and the main interneurons are ____. 80% of cortical neurons are ____, and 20% of the cortical neurons are ____. But, in the basal ganglia and cerebellum, ___ are the main projection cells. |
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Definition
The beta-gamma subunit of GABAB receptors modulate K+ and Ca2+ ion channels. The alpha subunits inhibits AC. In most parts of the brain, the main projection neurons are spiny glutamatergic neurons, and the main interneurons are GABAergic aspiny neurons. 80% of cortical neurons are excitatory (glutamatergic) spiny, pyramidal cells, and 20% of the cortical neurons are inhibitory (GABAergic) interneurons. But, in the basal ganglia and cerebellum, GABAergic cells are the main projection cells. |
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Term
| Typically, GABAergic interneurons within a forebrain area will receive similar inputs to the projection cells and provide _____ to them, or receive axon collaterals from the projection neurons, allowing _____. |
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Definition
| Typically, GABAergic interneurons within a forebrain area will receive similar inputs to the projection cells and provide feedforward inhibition to them, or receive axon collaterals from the projection neurons, allowing feedback inhibition. |
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Term
Therapeutic index= What is Rohypnol? Barbituates and benzodiazepines bind on distinct sites on... All sedative-hypnotics appear to enhance the ability of ___ to cause ___ influx through ___ receptors. |
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Definition
Therapeutic index=LD50/ED50. Rohypnol is a BZ. Barbituates and benzodiazepines bind to distinct sites on GABAA receptor. All sedative-hypnotics appear to enhance the ability of GABA to cause chloride influx through GABAA receptors. |
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Term
How do the effects of barbituates and benzodiazepines on GABAA channels differ? What are beta-carbolines? |
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Definition
GABAA+benzodiazepine makes GABAA channels open more frequently (as opposed to GABA alone). GABAA+barbituate makes GABAA channels stay open longer (as opposed to GABA alone).**Barbituates may also have some direct agonist effects** Beta-carbolines are inverse agonists at GABAA receptors (induce panic and anxiety) |
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Term
The alpha1 subunit of GABAA receptors are very important for... and the alpha2 subunit is very important for... |
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Definition
The alpha1 subunit of GABAA receptors is very important for sedative and amnesic effects of BZs. The alpha2 subunit is very important for anxiolytic effects. |
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Term
Why is less alcohol absorbed when person has eaten before drinking? Does the liver enzyme cytochrom p450 (microsomal ethanol oxidizing system) work more in rare drinkers of chronic drinkers? |
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Definition
Food in the stomach slows movement of alcohol into the intestine, so more alcohol gets degraded before being absorbed. Chronic drinkers...normally, only 5-10% of alcohol is metabolized by cytochrome p450, but in chronic drinkers 50-60% of alcohol is broken down by this microsomal ethanol oxidizing system. |
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Term
How is absinthe induce paradoxical effects? The structure of GHB is very similar to... Is GHB reliably self-administered by monkeys and rodents? |
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Definition
The alcohol enhances GABAA cloride currents but the thujuone is a GABAA antagonist, and therefore blocks the chloride current. The structure of GHB is very similar to GABA. GHB is not really reliably self-administered...mice prefer to drink low to med doses of GHB but they avoid high doses. |
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Term
GHB is cross-substituted with... What receptors does GHB work at? |
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Definition
GHB is cross-substituted with baclofen - a non-abused GABAB agonist (**is NOT cross-substituted with BZs, barbs, alcohol, opiates, or psychostimulants) GHB works at a GHB receptor as well as, with low affinity, at GABAB receptors (agonist) **mice with no GABAB receptors/given GHB receptor agonists,do not show GHB drug induced effects - GABAB receptor importan. |
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Term
Effect of low and high doses of GHB on midbrain DA neurons. Two drugs known as "dissociative anesthetics" |
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Definition
At low doses, GHB increases firing of midbrain DA neurons but at higher doses, the activity of these neurons decreases (b/c DA neurons have weaker GABAB to GIRK coupling than GABA cells). Ketamine and PCP are both dissociative anesthetics (trance-like, rather than sleep-like state). |
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Term
Effects of ____ are considered a useful model of schizophrenia - get both "positive" (psychosis) and "negative" (catatonia) symptoms. What kind of drug is PCP and Ketamine (what receptor do they act on etc) Where is the PCP binding site? The increased locomotor effects of PCP and Ketamine is dependent on |
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Definition
The effects of PCP are considered a useful model of schizophrenia. PCP and Ketamine are non-competitive NMDAr antagonists. PCP binding site is inside the NMDA ion channel..blocks ion flow. The increased locomotor effects of PCP and K is dependent on DA..no DA neurons=less locomotor activity with PCP or K. |
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Term
Are PCP and K self-administered by animals? Apoptosis can be triggered by either... What is Nabilone? |
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Definition
Yes, PCP and K are self-administered directly into the NAc by animals, which shows that the reinforcing effects of PCP and K are independent of DA. Apoptosis can be triggered either by NMDAr glutamate blockers or too much glutamate (excitotoxicity). Nabilone is a synthetic cannabinoid (antiemetic). |
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Term
What are they cannabinoid receptors (what kind are they)? Where are they found? Which is important for reward? |
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Definition
Cannabinoid receptors=CB1 and CB2 - Gi-coupled metabotropic receptors. CB2 is primarily found in the immune system while CB1 is found in the brain (presynaptic terminals)..exceptionally high densities in the basal ganglia, hippocampus, and cerebellum. CB1 receptors are important for reward - pretreatment with CB1 antagonists destroys self-administration of THC, alcohol, opioids, cocaine, nicotine...and less NAc DA release. |
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Term
What is Anandamide and what is 2-AG (1-arachidonoyl glycerol)? Endocannabinoids are important regulators of... ...they are typically synthesized in.... and serve as... |
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Definition
Anandamide is a partial cannabinoid agonist. 2-AG is a full CB1 agonist. Endocannabinoids are important regulators of synaptic transmission for both excitatory (glutamate) and inhibitory (GABA) synapses. Endocannabinoids are typically synthesized in the postsynaptic cell, and serve as a retrograde messenger. |
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Term
Cannabinoid retrograde signalling example: Glutamate overflow from active synapse activates ____. __ stimulates membrane bound ___. ___ produces IP3 and DAG. ___ converts DAG into ___. ___ diffuses to presynaptic side and acts as an ____ at ___ receptors. __ acts to reduce activity of _____ channels. |
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Definition
Glutamate overflow from active synapse activates mGluR5. Gq stimulates membrane bound PLCbeta (phospholipase Cbeta). PLCbeta produces IP3 and DAG. DGLalpha converts DAG into 2-AG. 2-AG diffuses to the presynaptic side and acts as an agonist at CB1 receptors. Gi acts to reduce the activity of voltage-gated Ca2+channels. |
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Term
Short-term decrease in presynaptic glutamate release. Short-term decrease in presynaptic GABA release. THC inhances DA release in... The analgesic effects of THC is due to action in... |
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Definition
Short-term decrease in presynaptic glutamate release= Depolarization-induced suppression of excitation (DSE) Short-term decrease in presynaptic GABA release= Depolarization-induced suppression of inhibition (DSI) THC inhances DA release in the NAc. The analgesic effects of THC is due to action in the spinal cord and peripheral tissue (via non-opiate mechanisms) |
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Term
THC tolerance in rats due to... Difference between opiate and opioid? What is Naloxone and Naltrexone? |
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Definition
THC tolerance in rats due to reduced CB1 receptor availability. Opiate=Natural...from Opium poppy Opioid=Natural and synthetic Naloxone and Naltrexone are competitive antagonists for opioids |
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Term
Opioids have a synergistic respiratory depression effect with... Depressing effects of opioids typically mask the stimulant-like effects but with direct injection into the ___, stimulant effect is clear. True/False: Both stimulant-like effects and opioid "reward" becomes sensitized with repeated use. |
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Definition
Opioids have a synergistic respiratory depression effect with sedative-hypnotics (e.g.alcohol). Depressing effects of opioids typically mask the stimulant-like effects but with direct injection into the VTA (area of midbrain DA cells) TRUE: Both stimulant-like effects and "reward" becomes sensitized with repeated opioid use. |
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Term
Abused opioids all bind to the __ receptor (though often not with high selectivity). All opioid receptors are ___. At GABA terminals, mu receptors are ___ and act to... At glutamate terminals , mu receptors are ___, and act to... |
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Definition
Abused opioids all bind to the mu-opioid receptor (though often not with high selectivity...morphine also binds to delta and kappa). All opioid receptors are metabotropic and coupled to Gi/o. At GABA terminals, my receptors are presynaptic and act to reduce synaptic transmission via inhibition of Ca2+ channels. At glutamate terminals, mu receptors are postsynaptic and act to inhibit cell by opening GIRKs. |
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